Trifluoroacetic acid → HCID 86673729, compound

HRID 576595Notes

Reaction equation

HRID 576595 reaction equation
[CH2:1]([C:4]1([CH:33]([CH3:35])[CH3:34])[CH2:8][CH:7]([OH:9])[N:6]([CH2:10][C:11]2[CH:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:14]=[CH:13][C:12]=2O[Si](C(C)C)(C(C)C)C(C)C)[C:5]1=[O:32])[CH:2]=[CH2:3].C(O)(C(F)(F)F)=O>C1COCC1.CCOC(C)=O>[CH2:1]([C:4]1([CH:33]([CH3:34])[CH3:35])[C:5](=[O:32])[N:6]2[CH:7]([O:9][C:12]3[CH:13]=[CH:14][C:15]([C:17]([F:18])([F:20])[F:19])=[CH:16][C:11]=3[CH2:10]2)[CH2:8]1)[CH:2]=[CH2:3]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57473830HCID 57473830, compound

Product 1

HCID 86673729HCID 86673729, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-allyl-5-hydroxy-3-isopropyl-1-(5-(trifluoromethyl)-2-(triisopropylsilyloxy)benzyl)pyrrolidin-2-one (approximately 525 mg, 1.02 mmol) in THF (13 mL) was charged with tris(dimethylamino)sulfonium difluorotrimethylsilicate (366 mg, 1.33 mmol) and the resulting mixture was stirred for 30 min. At this time the mixture was charged with TFA (0.394 mL, 5.11 mmol) and 4 angstrom molecular sieves (500 mg). This solution was stirred for 12 h, at which time it was diluted with EtOAc and washed 2× with brine. The organic layer was dried (MgSO4) and concentrated on a rotary evaporator. The residue was purified using a 12 g silica gel cartridge and 20:1 Hex/EtOAc to 3:1 Hex/EtOAc to elute 2-allyl-2-isopropyl-7-(trifluoromethyl)-2,3,3a,9-tetrahydro-1H-benzo[e]pyrrolo[2,1-b][1,3]oxazin-1-one (177 mg, 0.52 mmol, 51% yield) as a clear oil, 1:1 mixture of diastereomers. LC/MS [M+H]+=340.15, HPLC tR=1.99 min [Waters Sunfire C18 4.6×50 mm column, 3 min gradient from 10/90/0.1 MeOH/H2O/TFA to 90/10/0.1 MeOH/H2O/TFA at 4 mL/min flow rate]. 1H-NMR (400 MHz, CDCl3) δ=7.26 (d, J=8.0 Hz, 1H), 7.21 (s, 1H), 6.80 (d, J=8.0 Hz, 1H), 5.56 (m, 1H), 5.2-4.8 (m, 3H), 4.16 (m, 1H), 2.3-1.8 (m, 5H), 0.8-0.6 (m, 6H).

Workup

  1. stirringThis solution was stirred for 12 h, at which time it
  2. washwashed 2× with brine
  3. dry with materialThe organic layer was dried (MgSO4)
  4. concentrationconcentrated on a rotary evaporator
  5. customThe residue was purified
  6. washto elute

Sources & evidence

ORD record
ord-88a8de77361a4a83a2905f8c9c5cb19b
Source dataset
uspto-grants-2015_05
Patent number
US09040526B2

Reaction notes

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